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In less than a year, two influential articles reporting on consensus recommendations for therapy of “menopause-associated” and “menopausal” symptoms have been published (1) (JSOGC, February, 2006). Both of them conclude that estrogen (with or without progestin) is the optimal therapy. Both the Canadian (JSOGC, February, 2006) and the USA’s National Institutes of Health (1) statements recommend hormone therapy for symptomatic midlife women. The symptoms to which these statements primarily refer are hot flushes/night sweats (also called vasomotor symptoms or VMS) but the Canadian statement also specifically includes “mood swings.” Both statements recommend hormone therapy with as low a dose as possible and for as short a time as possible. I agree with that. However, I strongly disagree with estrogen therapy for hot flushes in perimenopause, when estrogen levels are still potentially high.

However, before I can explain why estrogen therapy should not be used for symptoms in perimenopause, I need to clarify what those two consensus statements are really saying, to make clear distinctions between the hot flushes that are difficult in perimenopause and those that need therapy in menopause, to discuss what we know about the risk factors for and life pattern of hot flushes for the women who experience them, and finally, to present the evidence showing that progesterone is effective for hot flushes.

First, what are the natural patterns of hot flushes? Almost two thirds of women have hot flushes/night sweats in the final year of perimenopause, these continue for two years on average, but have gone away for all except 10-20 percent in the five years following menopause (2). Women with the most hot flushes are those who are stressed (especially those who have trouble paying for basic needs like food and housing) and have lower education levels (3). Asian women living in the USA appear to have fewer hot flushes than Caucasian women and African American women to have more (3). Although, when occupation is similar for Caucasian and African American women, this racial difference disappears (4). It is now well documented that night sweats disturb sleep and that sleep problems worsen in perimenopause and may get better as women become menopausal (5). When sweats and flushes chronically waken a person, work effectiveness often suffers and there is a significant risk for developing depression (6).

A primer on midlife definitions and confusing language

With that background on night sweats and hot flushes, we can start to discuss the USA and Canadian consensus recommendations for “menopausal symptoms.” Both statements are (purposefully?) vague about what women should be treated for symptoms—“menopausal” and “menopause-associated” imply to most physicians, perimenopause as well as (post) menopause (one year without flow). What the consensus statements are saying is confusing because of the many meanings for the word “menopause.” Most women say they are “in menopause” when they start to experience anything that’s different. In other words, women say they are “in menopause” when they mean perimenopause. However, two official statements, define “menopause” as the literal final menstrual period (7;8). Yet, only when a year has passed without more flow is there a 95 percent probability that no more periods will occur (9). By that point, one year past the final period, estrogen levels are no longer thirty percent higher than normal, as they are in perimenopause, and have settled into their rather stable, normal low levels (10).

Although estrogen is the strongest known therapy for hot flushes in menopausal women, decreasing their number by 77% (18), there is strong evidence that synthetic cousins of progesterone are also effective. Medroxyprogesterone, like estrogens, is effective for hot flush control in the best kind of scientific study, the randomized placebo-controlled trial (19;20). However, the literature contains very few reports in which estrogen is tested against progestin for hot flush control in the same trial. Two studies that were randomized but both women and scientists knew who was taking what, tested high levels of estrogen similar to those in birth control pills against male-hormone derived progestins (21;22). Estrogen and estrogen/norgestrel (a progestin) were more effective than norgestrel alone, but all of the therapies including any hormone were more effective than placebo (21). Norethindrone, another progestin, however, was less effective than either of two high estrogen doses and not different from placebo (22). In a better, blinded, randomized controlled trial we tested conjugated equine estrogen (Premarin 0.6 mg/day) against medroxyprogesterone (Provera, 10 mg/d) and showed that they were equally effective (23). The large study comparing all controlled trials of estrogen against placebo, also showed that estrogen with progestin was even stronger than estrogen alone—combined hormones decreased hot flushes by about 90% (18).

Progesterone has a “side effect” that it significantly improves deep sleep (28) thus particularly helping night sweats and one of the major reasons VMS interfere with women’s well being. (Progesterone cream and progestins don’t help sleep).

Stopping estrogen therapy causes a rebound increase in the number and severity of hot flushes and night sweats to greater than they were initially (29). There is no evidence from clinical experience (although the definitive study has not yet been done) that stopping progesterone or progestin leads to a similar rebound increase in VMS.

WHO Technical Report Series. Research on the menopause in the 1990's. A report of the WHO Scientific Group. 866, 1-107. 1996. World Health Organization, Geneva, Switzerland, World Health Organization. Ref Type: Report

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